Particulate Matter Induces Translocation of IL-6 from the Lung to the Systemic Circulation
- 1 February 2011
- journal article
- Published by American Thoracic Society in American Journal of Respiratory Cell and Molecular Biology
- Vol. 44 (2), 197-204
- https://doi.org/10.1165/rcmb.2009-0427oc
Abstract
The biological mechanisms responsible for an association between elevated concentrations of ambient particulate matter (PM) and increased cardiovascular morbidity and mortality remain unclear. Our laboratory showed that exposure to PM induces systemic inflammation that contributes to vascular dysfunction. This study was designed to determine whether the lung is a major source of systemic inflammatory mediators, using IL-6 as a surrogate marker. We also sought to determine the impact on vascular dysfunction after exposure to PM of less than 10 μm in diameter (PM(10)). C57BL/6 mice were intratracheally exposed to a single instillation of PM(10) (10 or 200 μg) or saline. Four hours or 24 hours after exposure, venous and arterial blood samples were simultaneously collected from the right atrium and descending aorta. Concentrations of IL-6 were measured in bronchoalveolar lavage fluid (BALF) and serum samples. Vascular functional responses to acetylcholine (ACh) and phenylephrine were measured in the abdominal aorta. Concentrations of IL-6 in BALF samples were increased at 4 and 24 hours after exposure to PM(10). At baseline, concentrations of IL-6 in venous blood were higher than those in arterial blood. Exposure to PM(10) reversed this arteriovenous gradient, 4 hours after exposure. The relaxation responses of the abdominal aorta to ACh decreased 4 hours after exposure to 200 μg PM(10). In IL-6 knockout mice, the instillation of recombinant IL-6 increased IL-6 concentrations in the blood, and exposure to PM(10) did not cause vascular dysfunction. These results support our hypothesis that exposure to PM(10) increases pulmonary inflammatory mediators that translocate to the circulation, contributing to systemic inflammation, with downstream effects such as vascular dysfunction.Keywords
This publication has 50 references indexed in Scilit:
- Direct Impairment of Vascular Function by Diesel Exhaust Particulate through Reduced Bioavailability of Endothelium-Derived Nitric Oxide Induced by Superoxide Free RadicalsEnvironmental Health Perspectives, 2009
- Air Pollution Exposure Potentiates Hypertension Through Reactive Oxygen Species-Mediated Activation of Rho/ROCKArteriosclerosis, Thrombosis, and Vascular Biology, 2008
- Particulate matter exposure induces persistent lung inflammation and endothelial dysfunctionAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2008
- Endothelial Function and Chronic Exposure to Air Pollution in Normal Male SubjectsHypertension, 2007
- Ambient particulate matter accelerates coagulation via an IL-6–dependent pathwayJCI Insight, 2007
- Inter-relationships of indices of endothelial damage/dysfunction [circulating endothelial cells, von Willebrand factor and flow-mediated dilatation] to tissue factor and interleukin-6 in acute coronary syndromesInternational Journal of Cardiology, 2005
- Vascular effects of ambient particulate matter instillation in spontaneous hypertensive ratsToxicology and Applied Pharmacology, 2004
- Interleukin-6 Induces Oxidative Stress and Endothelial Dysfunction by Overexpression of the Angiotensin II Type 1 ReceptorCirculation Research, 2004
- Systemic Effects of Inhaled Ultrafine Particles in Two Compromised, Aged Rat StrainsInhalation Toxicology, 2004
- Paradoxical Vasoconstriction Induced by Acetylcholine in Atherosclerotic Coronary ArteriesNew England Journal of Medicine, 1986